The developing nervous system is among the most vulnerable targets of ethanol. Unlike other organs, the brain develops over a protracted period. It is susceptible to ethanol toxicity from its inception (at gastrulation), through gestation, infancy, and adolescence. We will focus on the effects of ethanol exposure during the fetal/neonatal and adolescent periods because they are (1) times of critical and rapid brain growth and (2) when developing humans are most likely exposed to ethanol, i.e., times of prime clinical relevancy. Indeed, fetal and adolescent exposures are key risk factors for alcoholism in adults. In turn, adult alcoholics produce children with fetal alcohol spectrum disorder and adolescents predisposed to early initiation into alcohol use. This increases adolescents'susceptibility to developing alcohol use disorders, and hence perpetuates the cycle. This developmental programming constitutes what we have dubbed the "alcoholism generator." The binding themes of our Developmental Exposure Alcohol Research Center (DEARC) are (1) that ethanol affects neuroadaptation in the developing nervous system, (2) that ethanol-induced effects depend upon the developmental stage of the nervous system, and (3) common mechanisms by which brain development alters the effects of ethanol and conversely ethanol affects brain development. The themes of the DEARC bind the novel hypotheses raised in each project. Four highly integrated Main Projects will examine mechanisms of ethanol-related developmental defects. These projects are studies of the effects of developmental exposure to ethanol during the prenatal/infant or adolescent periods (1) on the fates of neural stem cells and dendritic plasticity, (2) on experience-induced plasticity in chemosensory function and development, (3) on ontogenetic programming and age-related mechanisms of positive and negative ethanol reinforcement, and (4) on the role of neurotransmitter systems in adolescent-typical ethanol sensitivities. Senior alcohol researchers and developmental neurobiologists will direct these projects. The grease and glue underpinning the synergistic interactions among these investigators comes from the Administrative Core and three scientific cores (Animal, Cell/Molecular Biology, and Neuroanatomy Cores). The center will continue to serve as an incubator for ideas, new projects, and the growth of investigators. One mechanism for these activities will be the Pilot Project Program. The proposed pilot projects will complement and extend the Main Projects. As a unit, the proposed center will meld the talents of senior biomedical and behavioral researchers at three campuses of the State University of New York: Binghamton University in Binghamton, SUNY-Cortland, and Upstate Medical University in Syracuse. Thus, the DEARC will serve as a nexus of alcohol research in Central New York and as a beacon for national activities.